title: Peptidoglycan recognition protein 1 promotes house dust mite-induced airway inflammation in mice.
abstract: Peptidoglycan recognition protein (Pglyrp) 1 is a pattern-recognition protein that mediates antibacterial host defense. Because we had previously shown that Pglyrp1 expression is increased in the lungs of house dust mite (HDM)-challenged mice, we hypothesized that it might modulate the pathogenesis of asthma. Wild-type and Pglyrp1(-/-) mice on a BALB/c background received intranasal HDM or saline, 5 days/week for 3 weeks. HDM-challenged Pglyrp1(-/-) mice showed decreases in bronchoalveolar lavage fluid eosinophils and lymphocytes, serum IgE, and mucous cell metaplasia, whereas airway hyperresponsiveness was not changed when compared with wild-type mice. T helper type 2 (Th2) cytokines were reduced in the lungs of HDM-challenged Pglyrp1(-/-) mice, which reflected a decreased number of CD4(+) Th2 cells. There was also a reduction in C-C chemokines in bronchoalveolar lavage fluid and lung homogenates from HDM-challenged Pglyrp1(-/-) mice. Furthermore, secretion of CCL17, CCL22, and CCL24 by alveolar macrophages from HDM-challenged Pglyrp1(-/-) mice was markedly reduced. As both inflammatory cells and airway epithelial cells express Pglyrp1, bone marrow transplantation was performed to generate chimeric mice and assess which cell type promotes HDM-induced airway inflammation. Chimeric mice lacking Pglyrp1 on hematopoietic cells, not structural cells, showed a reduction in HDM-induced eosinophilic and lymphocytic airway inflammation. We conclude that Pglyrp1 expressed by hematopoietic cells, such as alveolar macrophages, mediates HDM-induced airway inflammation by up-regulating the production of C-C chemokines that recruit eosinophils and Th2 cells to the lung. This identifies a new family of innate immune response proteins that promotes HDM-induced airway inflammation in asthma.
authors.affiliation: 1 Cardiovascular and Pulmonary Branch.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Yao
authors.forename: Meixia
authors.initials: M
authors.lastname: Gao
authors.forename: Cuilian
authors.initials: C
authors.lastname: Dai
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Meyer
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Keeran
authors.forename: Gayle Z
authors.initials: GZ
authors.lastname: Nugent
authors.forename: Xuan
authors.initials: X
authors.lastname: Qu
authors.forename: Zu-Xi
authors.initials: ZX
authors.lastname: Yu
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dagur
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Levine
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D019742:Chemokines, CC / Q000096:biosynthesis; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D019742:Chemokines, CC; D016207:Cytokines; C113582:Pglyrp1 protein, mouse